The main objective of this project is to examine the role of SV40 in malignant transformation of human cells. SV40 is a simian virus that can transform mammalian cells from many species to the malignant state. Rodent cells transformed by this virus are generally tumorigenic in immunologically permissive experimental hosts such as the athymic nude mouse, but primate (human and monkey) cells similarly transformed in culture have been found to be nontumorigenic. Available evidence indicates that, at least for some of the human cell lines transformed by SV40, their inability to form growing tumors in nude mice is due to a host rejection mechanism that is as yet poorly understood. The following questions are being examined: (1)\the nature of thymus-independent host mechanisms responsible for the tumor rejection; (2)\identity of the SV40-induced cellular antigens responsible for eliciting the host rejection response; and (3)\the molecular domain of the SV40 T-antigen gene that codes for the minimal antigen needed to elicit the tumor rejection in the athymic host.